Calcium chelate and gadolinium pharmaceutical composition and methods of x-ray and nmr imaging

Abstract

Improved metal complex-containing pharmaceutical agents are described which, as an additive, contain one or more complexing agents and/or one or more weak metal complex(es) or mixtures thereof.

What is claimed is: 
     
       1. A pharmaceutical composition comprising a diagnostically effective amount of the gadolinium chelate complex of N 6  -carboxymethyl-N 3 ,N 9  -bis(methylcarbamoyl-methyl)-3,6,9-triazaundecanedioic acid, a pharmaceutically acceptable carrier and 2-10 mole % of a sodium salt of a calcium chelate complex, based on the amount of said gadolinium chelate complex, up to a maximum of 50 mmol/l of said composition, wherein said amount of calcium chelate complex is effective to enhance the safety in a human of said composition with respect to an identical composition except lacking said calcium chelate complex. 
     
     
       2. A composition of claim 1, wherein the amount of said sodium salt of a calcium chelate complex is 2-6 mole %. 
     
     
       3. A composition of claim 1 which is sterile. 
     
     
       4. A composition of claim 1, wherein said amount of sodium salt of a calcium chelate complex is up to a maxium of 30 mmol/l of said composition. 
     
     
       5. A composition of claim 1, wherein the amount of said gadolinium complex is between 1 micromole and 1 mole per liter. 
     
     
       6. A composition of claim 1, wherein the chelating agent of said sodium salt of a calcium chelate complex is the same as that of said gadolinium chelate complex. 
     
     
       7. A composition of claim 1, wherein the chelating agent of said sodium salt of a calcium chelate complex is different from that of said gadolinium chelate complex. 
     
     
       8. A method of obtaining an NMR image, comprising administering to a patient, of whom said image is to be obtained, a diagnostically effective amount of a pharmaceutical composition comprising a diagnostically effective amount of the gadolinium chelate complex of N 6  carboxymethyl-N 3 ,N 9  -bis(methylcarbamoylmethyl)3,6,9-troazaimdecamedopoc acid, a pharmaceutically acceptable carrier and 2-10 mole % of a sodium salt of a calcium chelate complex, based on the amount of said gadolinium chelate complex, up to a maximum of 50 mmol/l of said composition, wherein said amount of calcium chelate complex is effective to enhance the safety in a human of said composition with respect to an identical composition except lacking said calcium chelate complex, and taking said image. 
     
     
       9. A method of claim 8, wherein the amount of said sodium salt of a calcium chelate complex is 2-6 mole %. 
     
     
       10. A method of claim 8, wherein said composition is sterile. 
     
     
       11. A method of claim 8, wherein said amount of sodium salt of a calcium chelate complex is up to a maximum of 30 mmol/l of said composition. 
     
     
       12. A method of claim 8, wherein said amount of said gadolinium complex in said composition is between 1 micromole and 1 mole per liter. 
     
     
       13. A method of claim 8, wherein the chelating agent of said sodium salt of a calcium chelate complex is the same as that of said gadolinium chelate complex. 
     
     
       14. A method of claim 8, wherein the chelating agent of said sodium salt of a calcium chelate complex is different from that of said gadolinium chelate complex. 
     
     
       15. A method of claim 8, wherein the amount of the gadolinium chelate complex administered is between 0.001 and 5 mmol/kg. 
     
     
       16. A method of obtaining an X-ray image, comprising administering to a patient, of whom said image is to be obtained, a diagnostically effective amount of a pharmaceutical composition comprising a diagnostically effective amount of the gadolinium chelate complex of N 6  carboxymethyl-N 3 ,N 9  -bis(methylcarbamoylmethyl)-3,6,9-triazaundecanedioic acid, a pharmaceutically acceptable carrier and 2-10 mole % of a sodium salt of a calcium chelate complex, based on the amount of said gadolinium chelate complex, up to a maximum of 50 mmol/l of said composition, wherein said amount of calcium chelate complex is effective to enhance the safety in a human of said composition with respect to an identical composition except lacking said calcium chelate complex, and taking said image. 
     
     
       17. A method of claim 16, wherein the amount of said sodium salt of a calcium chelate complex is 2-6 mole %. 
     
     
       18. A method of claim 16, wherein said composition is sterile. 
     
     
       19. A method of claim 16, wherein said amount of sodium salt of a calcium chelate complex is up to a maximum of 30 mmol/l of said composition. 
     
     
       20. A method of claim 16, wherein the amount of said gadolinium complex in said composition is between 1 micromole and 1 mole per liter. 
     
     
       21. A composition of claim 16, wherein the chelating agent of said sodium salt of a calcium chelate complex is the same as that of said gadolinium chelate complex. 
     
     
       22. A method of claim 16, wherein the chelating agent of said sodium salt of a calcium chelate complex is different from that of said gadolinium chelate complex. 
     
     
       23. A method of claim 16, wherein the amount of the gadolinium chelate complex administered is between 0.001 and 5 mmol/kg. 
     
     
       24. A composition of claim 1, wherein said amount of sodium salt of a calcium chelate complex is 2-6 mole % based on the amount of said gadolinium chelate complex and is up to a maximum of 30 mmol/l of said composition, and wherein the chelating agent of said sodium salt of a calcium chelate complex is the same as that of said gadolinium chelate complex. 
     
     
       25. A method of claim 8, wherein said amount of sodium salt of a calcium chelate complex is 2-6 mole % based on the amount of said gadolinium chelate complex and is up to a maximum of 30 mmol/l of said composition, and wherein the chelating agent of said sodium salt of a calcium chelate complex is the same as that of said gadolinium chelate complex.